A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors

A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors

The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Endometrial Cancer; Solid Tumors; Biliary Tract Cancer (BTC); Colorectal Cancer (CRC); Gastroesophageal Cancer (GC)
• Intervention / Treatment: Drug: INCB001158; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Gemcitabine; Drug: Cisplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 6000
    • Grand Hopital de Charleroi - Department of Medical Oncology
  • Brussels, Belgium, B-1000
    • Institut Jules Bordet - Clinical Trials Conduct Unit
• United Kingdom
  • London, United Kingdom, WC1E 6BT
    • UCL Cancer Institute
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama
    • Mobile, Alabama, United States, 36604
      • USA Mitchell Cancer Center
  • California
    • Sacramento, California, United States, 95817
      • UC Davis - Comprehensive Cancer Centre
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • START San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
• Presence of measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen.
• Resolution of treatment-related toxicities.
• Adequate hepatic, renal, cardiac, and hematologic function.
• Additional cohort-specific criteria may apply.

Exclusion Criteria:

• Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
• Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug.
• Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment.
• Has received prior approved radiotherapy within 14 days of study therapy.
• Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has an active infection requiring systemic therapy.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group A; INCB001158 + FOLFOX	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Names: Arginase inhibitor; Drug: Oxaliplatin; Oxaliplatin administered intravenously at the protocol-defined dose and schedule.; Drug: Leucovorin; Leucovorin at the protocol-defined dose and regimen.; Drug: 5-Fluorouracil; 5-Fluorouracil at the protocol-defined dose and regimen.
Experimental: Treatment Group B; INCB001158 + gemcitabine/cisplatin	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Names: Arginase inhibitor; Drug: Gemcitabine; Gemcitabine at the protocol-defined dose and regimen.; Drug: Cisplatin; Cisplatin at the protocol-defined dose and regimen.
Experimental: Treatment Group C; INCB001158 + paclitaxel	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Names: Arginase inhibitor; Drug: Paclitaxel; Paclitaxel at the protocol-defined dose and regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.	up to 1385 days
Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)	A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.	up to Day 28
Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen	The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.	up to Day 580
Phase 2: Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.	up to 1385 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: ORR	ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, as determined by investigator assessment of radiographic disease as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the Baseline sum diameters, no new lesions, and no progression of non-target lesions.	up to 580 days
Phases 1 and 2: Duration of Response	DOR was defined as the time from initial objective response (CR or PR) (as determined by investigator assessment of radiographic disease assessment per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if it occurred sooner than disease progression. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.	up to 368 days
Phases 1 and 2: Disease Control Rate	DCR was defined as the percentage of participants with an overall response of CR, PR, or stable disease (SD), as determined by investigator assessment of radiographic disease as per RECIST v1.1, for at least 8 weeks. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.	up to 1385 days
Phases 1 and 2: Progression-free Survival	According to RECIST 1.1, PFS was defined as the length of time from the date of the first dose study of drug until the earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death due to any cause, if it occurred sooner than progression.	up to 1385 days
Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration	Cmin was defined as the minimum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.	Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection
Cmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration	Cmax was defined as the maximum observed plasma concentration over the dose interval. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.	Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Tmax of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration	tmax was defined as the time to the maximum concentration. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.	Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
AUC0-t of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration	AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.	Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection
Tlast of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy Following the First Dose on Cycle 1 Day 1 and on Cycle 2 Day 1 Following Repeated Dose Administration	tlast was defined as the time of the last sample collected from which a concentration was measured. Extensive sample collection was used for the first 12 participants enrolled in each chemotherapy regimen. Sparse sample collection was used for the 13th participant enrolled and onward.	Day 1 of Cycles 1 and 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycles 1 and 2: predose; 1 and 4 hours post-dose for sparse sample collection

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Lance Leopold, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): November 28, 2022
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: cisplatin; colorectal cancer; oxaliplatin; endometrial cancer; paclitaxel; ovarian cancer; solid tumors; gemcitabine; leucovorin; biliary tract cancer; gastroesophageal cancer; 5 fluorouracil; INCB001158; arginase inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Biliary Tract Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Colorectal Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Paclitaxel; Fluorouracil; Oxaliplatin; Leucovorin; Gemcitabine
• Other Study ID Numbers: INCB 01158-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No